Title | Beta-lactamase inhibitors derived from single-domain antibody fragments elicited in the camelidae. |
Publication Type | Journal Article |
Year of Publication | 2001 |
Authors | Conrath, K. E., M. Lauwereys, M. Galleni, A. Matagne, J. M. Frère, J. Kinne, L. Wyns, and S. Muyldermans |
Journal | Antimicrob Agents Chemother |
Volume | 45 |
Issue | 10 |
Pagination | 2807-12 |
Date Published | 2001 Oct |
ISSN | 0066-4804 |
Keywords | Amino Acid Sequence, Ampicillin, Animals, Antibody Specificity, Bacterial Proteins, beta-Lactamases, Camels, Escherichia coli, Immunoglobulin Fragments, Male, Molecular Sequence Data, Penicillin Resistance, Penicillins, Protein Structure, Tertiary, Sequence Homology, Amino Acid |
Abstract | Small, soluble single-domain fragments derived from the unique variable region of dromedary heavy-chain antibodies (VHHs) against enzymes are known to be potent inhibitors. The immunization of dromedaries with the TEM-1 and BcII beta-lactamases has lead to the isolation of such single-domain antibody fragments specifically recognizing and inhibiting those beta-lactamases. Two VHHs were isolated that inhibit TEM-1 and one BcII inhibiting VHH was identified. All inhibitory VHHs were tight-binding inhibitors. The 50% inhibitory concentrations were determined for all inhibitors and they were all in the same range as the enzyme concentration used in the assay. Addition of the VHHs to the TEM-1 beta-lactamase, expressed on the surface of bacteria, leads to a higher ampicillin sensitivity of the bacteria. This innovative strategy could generate multiple potent inhibitors for all types of beta-lactamases. |
DOI | 10.1128/AAC.45.10.2807-2812.2001 |
Alternate Journal | Antimicrob. Agents Chemother. |
PubMed ID | 11557473 |
PubMed Central ID | PMC90735 |
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